5-76295885-C-G

Variant names:

• chr5-76295885-C-G
• rs2270927
• NM_014979.4:c.1445C>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_014979.4(SV2C):​c.1445C>G​(p.Thr482Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,612,150 control chromosomes in the GnomAD database, including 12,779 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.16 (2350 hom., cov: 32)
  • Exomes 𝑓: 0.11 (10429 hom.)
• Consequence: SV2C NM_014979.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.356
• Publications: 25 publications found

Genes affected

SV2C (HGNC:30670): (synaptic vesicle glycoprotein 2C) Predicted to enable transmembrane transporter activity. Predicted to be involved in chemical synaptic transmission; neurotransmitter transport; and transmembrane transport. Predicted to be located in plasma membrane and synaptic vesicle. Predicted to be active in neuron projection and synaptic vesicle membrane. Predicted to be integral component of synaptic vesicle membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000250348 (HGNC:58251):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0033721626).
• BP6: Variant 5-76295885-C-G is Benign according to our data. Variant chr5-76295885-C-G is described in ClinVar as Benign. ClinVar VariationId is 3059133.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014979.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SV2C	NM_014979.4	MANE Select	c.1445C>G	p.Thr482Ser	missense	Exon 9 of 13	NP_055794.3
	SV2C	NM_001297716.2		c.1445C>G	p.Thr482Ser	missense	Exon 9 of 13	NP_001284645.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SV2C	ENST00000502798.7	TSL:1 MANE Select	c.1445C>G	p.Thr482Ser	missense	Exon 9 of 13	ENSP00000423541.2
	SV2C	ENST00000322285.7	TSL:2	c.1445C>G	p.Thr482Ser	missense	Exon 9 of 13	ENSP00000316983.7
	SV2C	ENST00000506257.1	TSL:3	n.200C>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24383 AN: 152018 Hom.: 2338 Cov.: 32

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.0979

Gnomad OTH AF: 0.149

GnomAD2 exomes AF: 0.141 AC: 34937 AN: 248140 AF XY: 0.137

Gnomad AFR exome AF: 0.269

Gnomad AMR exome AF: 0.191

Gnomad ASJ exome AF: 0.208

Gnomad EAS exome AF: 0.180

Gnomad FIN exome AF: 0.121

Gnomad NFE exome AF: 0.101

Gnomad OTH exome AF: 0.126

GnomAD4 exome AF: 0.112 AC: 163560 AN: 1460014 Hom.: 10429 Cov.: 31 AF XY: 0.112 AC XY: 81674 AN XY: 726280

African (AFR) AF: 0.270 AC: 9017 AN: 33392

American (AMR) AF: 0.189 AC: 8409 AN: 44408

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 5392 AN: 26074

East Asian (EAS) AF: 0.201 AC: 7946 AN: 39612

South Asian (SAS) AF: 0.138 AC: 11860 AN: 86008

European-Finnish (FIN) AF: 0.118 AC: 6315 AN: 53354

Middle Eastern (MID) AF: 0.144 AC: 829 AN: 5752

European-Non Finnish (NFE) AF: 0.0959 AC: 106507 AN: 1111100

Other (OTH) AF: 0.121 AC: 7285 AN: 60314

GnomAD4 genome AF: 0.161 AC: 24421 AN: 152136 Hom.: 2350 Cov.: 32 AF XY: 0.164 AC XY: 12228 AN XY: 74366

African (AFR) AF: 0.264 AC: 10972 AN: 41512

American (AMR) AF: 0.177 AC: 2702 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 729 AN: 3472

East Asian (EAS) AF: 0.180 AC: 932 AN: 5184

South Asian (SAS) AF: 0.134 AC: 646 AN: 4824

European-Finnish (FIN) AF: 0.126 AC: 1328 AN: 10562

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.0979 AC: 6657 AN: 68004

Other (OTH) AF: 0.147 AC: 310 AN: 2108

Alfa AF: 0.0972 Hom.: 279

Bravo AF: 0.168

TwinsUK AF: 0.102 AC: 380

ALSPAC AF: 0.106 AC: 409

ESP6500AA AF: 0.258 AC: 949

ESP6500EA AF: 0.101 AC: 821

ExAC AF: 0.140 AC: 16957

Asia WGS AF: 0.191 AC: 662 AN: 3478

EpiCase AF: 0.0995

EpiControl AF: 0.0994

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	SV2C-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.038	T
MetaRNN	Benign	0.0034	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.36
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.18
Sift	Benign	0.27	T
Sift4G	Benign	0.49	T
Polyphen		0.0	B
Vest4		0.014
MutPred		0.20		Gain of ubiquitination at K477 (P = 0.1204)
MPC		0.13
ClinPred		0.0090	T
GERP RS		0.66
Varity_R		0.17
gMVP		0.61
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2270927; hg19: chr5-75591710; COSMIC: COSV59231890;